1. Field of the Invention
This invention generally relates to biological analyte measurement and, more particularly, to a method for functionalizing a multiple-analyte transducer microarray.
2. Description of the Related Art
Microarray technology is a power research tool that permits the assaying of multiple analytes in a single sample—a multiplexed assay format. To perform such assay, a microarray has to contain multiple transducers modified with different bio-components. Selective attachment of a desired bio-component to a particular transducer constitutes one of the biggest challenges in the microarray technology. At present, the major approaches for microarray multiplexing are: (i) spotting of different bio-components over an array; (ii) physical separation of transducers via a nano-fluidic set of connections, and target delivery of bio-components to pre-selected transducers; (iii) self-assembling of tagged bio-components on an array surface that is modified with an agent capable of the specific capturing of bio-component tags; and (iv) controlled synthesis of bio-components on the surface of transducers. All these approaches have limitations in terms of costs and ease of mass manufacturing.
The spotting technology approach (i) is based on the target delivery of certain bio-components to selected transducers (spots) on the array, followed by attachment to the array surface. The spotting approach has serious limitations regarding the size and shape of the transducers that can be used. The approach of controlled delivery of bio-components (ii) to selected transducers on the array via micro, or a nano-fluidic set of connections, requires expensive instrumentation. The self assembling technology (iii) converts an oligonucleotide array into an immuno-array by using bio-components (antibodies) modified with specific oligonucleotide tags (K. Dill, K. Schwarzkopf, and A. Ghindilis, Multiplexed Analyte and Oligonucleotide Detection on Microarrays Using Several Redox Enzymes in Conjunction With Electrochemical Detection, Lab on a Chip, (2006) 6, 1052-1055). The specific hybridization of bio-component tags with array oligonucleotide probes results in immobilization on the surface of array transducers. The advantage of the approach is the simplicity of a one-stage procedure of array conversion. However, the technology requires very expensive semiconductor-based in situ synthesized oligonucleotide arrays. The approach of controlled synthesis of bio-components (iv) on the array surface is based on photolithography (Affymetrix®), ink-jet printing (Agilent Technologies), or electrochemistry (CombiMatrix). In all cases, a multi-stage process is used in the control of phosphoamidite chemistry by manipulation with a blocking agent on each array transducer. At present, this approach is only applicable for in situ synthesis of oligonucleotide arrays, and the synthesis itself is quite expensive.
It would be advantageous if there was a simpler and more cost-effective way for the attachment of bio-components onto selected transducers of a multi-analyte microarray.